大矢 一登

統合失調症患者では,個々の患者で程度はさまざまであるものの,認知機能の低下が生じることが報告されてきた.本研究の目的は,統合失調症患者の病前知能と現在の知的機能から推定された認知機能障害の程度を調査することである.11の大学病院などからリクルートされた,446名の統合失調症患者と686名の健常者に日本版WAIS-III成人知能検査,知的機能の簡易評価(JART)の25項目短縮版を実施し,現在の知的能力と病前推定知能を評価した.現在の知的能力と病前推定知能の差から認知機能障害スコアを算出した.統合失調症患者での推定認知機能障害スコアは-16.3,現在の知的機能が84.2,病前推定知能は100.5であり,いずれの項目においても,健常者と比較して有意に低かった.さらに,推定認知機能障害スコアで20以上の低下を示した患者の割合は39.7%であった.推定認知機能障害スコアを用いると,81.6%の患者と健常者を正しく判別することができた.本研究によって,統合失調症患者の認知機能障害の程度とその分布が明らかとなった.このような知見は,認知機能障害をもつ患者を同定し,認知機能障害の重症度の評価をするうえで寄与しうるものである.(著者抄録)

Background: The relative efficacy and tolerability of antipsychotics for schizophrenia are considerably well studied. This study aimed to examine whether previous findings could be replicated in a genetically distinct and homogenous group (ie, Japanese patients with schizophrenia) and whether previous findings could be extended to a broader range of antipsychotics with previously unclear relative efficacy and tolerability. Methods: Bayesian network meta-analysis was performed in which randomized trials comparing any of the following interventions were included: second-generation antipsychotics, haloperidol, or placebo. The primary outcomes for efficacy and acceptability were the response rate and all-cause discontinuation. The secondary outcomes included the improvement of Positive and Negative Syndrome Scale scores, discontinuation because of adverse events, and individual adverse events. Results: Eighteen relevant studies were identified (total n=3,446; aripiprazole =267, blonanserin =285, clozapine =47, clocapramine =295, haloperidol =857, mosapramine =493, olanzapine =179, paliperidone =136, perospirone =146, placebo =138, quetiapine =212, and risperidone =338; mean study duration =8.33 +/- 1.41 weeks). In primary outcomes, olanzapine and paliperidone showed efficacy than placebo, and olanzapine and paliperidone showed superior acceptability compared with placebo. There were differences in the incidences of individual adverse events (the best antipsychotic: extrapyramidal symptoms = olanzapine, hyperprolactinemia-related symptoms = quetiapine, sedation = paliperidone, and weight change = blonanserin) among antipsychotics. Conclusion: Although the current analysis exclusively included Japanese patients with schizophrenia, no remarkable differences were observed in efficacy and safety compared with previous meta-analyses. Diverse hierarchies in safety outcomes also support the implication that individual risk expectations for adverse events can guide clinical decisions. However, the sample size was relatively limited. Additional efficacy and safety data are required to fully obtain a conclusive understanding.

This meta-analysis of randomized controlled trials aimed to examine the advantages of long-acting injectable antipsychotics over placebo or oral medications regarding efficacy and safety for patients with bipolar disorder. Two categorical meta-analyses of randomized controlled trials were performed to compare study-defined relapse rate (primary), discontinuation rates, and individual adverse events: (1) risperidone-long-acting injectable vs placebo, and (2) long-acting injectable antipsychotics vs oral medications. We identified 7 randomized controlled trials (n=1016; long-acting injectable antipsychotics [flupenthixol (1 randomized controlled trial) and risperidone (6 randomized controlled trials)=449]; oral medications [mood stabilizers, antidepressants, antipsychotic, or any combination of these agents=283]; and placebo=284). Risperidone-long-acting injectable antipsychotic was superior to placebo for study-defined relapse rate (risk ratio=0.63, P <.0001), relapse of manic symptoms (risk ratio=0.42, P <.00001), and all-cause discontinuation (risk ratio=0.75, P=.007). Risperidone-long-acting injectable was associated with higher incidence of prolactin-related adverse events (risk ratio=4.82, P=.001) and weight gain (risk ratio=3.80, P <.0001) than placebo. The pooled long-acting injectable antipsychotics did not outperform oral medications regarding primary outcome but with significant heterogeneity (I-2=74%). Sensitivity analysis, including only studies with rapid cycling or high frequency of relapse patients, revealed that long-acting injectable antipsychotics were superior compared to oral medications (I-2=0%, RR=0.58, P=.0004). However, the comparators in this sensitivity analysis did not include second-generation antipsychotic monotherapy. In sensitivity analysis, including only studies with second-generation antipsychotic monotherapy as the comparator, long-acting injectable antipsychotics did not outperform second-generation antipsychotic monotherapy. Risperidone-long-acting injectable was also associated with higher incidence of prolactin-related adverse events than oral medications (RR=2.66, P=.03). Long-acting injectable antipsychotics appear beneficial for relapse prevention in patients with rapid cycling. Furthermore, randomized controlled trials comparing long-acting injectable antipsychotics and oral second-generation antipsychotic using larger samples of rapid cycling patients are warranted.

This study aimed to perform a comprehensive meta-analysis of topiramate-augmentation therapy in patients with schizophrenia receiving antipsychotic agents. Data published up to June 20, 2016 were obtained from the PubMed, PsycINFO, and Cochrane Library databases. Twelve randomized controlled trials comparing topiramate to placebo or antipsychotic only were included (n=676 patients). The primary outcome was change in overall symptoms. Relative risk (RR) and standardized mean difference (SMD), along with 95% confidence intervals, were calculated using random effects model for each outcome. Topiramate-augmentation therapy was superior to the control for decreasing overall symptoms (SMD -0.55, 95% confidence interval -0.86 to -0.24; P= 0.001; I-2 = 55%, eight comparisons, n= 380), positive symptoms (SMD -0.4), negative symptoms (SMD -0.47), and Positive and Negative Syndrome Scale general subscale scores (SMD -0.67). Furthermore, topiramate-augmentation therapy decreased weight (SMD -0.69) and body mass index (SMD -0.95) compared with the control. Topiramate was similar to the control with respect to discontinuation due to all causes (RR 1.19), inefficacy (RR 1.71), and adverse events (RR 1.09). Topiramate was associated with higher incidence of paresthesia (RR 2.67) and attention difficulty (RR 8.97) compared with the control. Our results seemed to suggest that topiramate-augmentation therapy improves the psychopathology of schizophrenia with good tolerability and has the additional advantage of weight maintenance. However, because there were some limitations (numbers of studies and patients included in the meta-analysis were small, some studies used completer analysis, Chinese studies were included in the meta-analysis, and studies that had a risk of bias were included in the meta-analysis) in this study, we cannot apply the results of this study in daily clinical practice.

Background: There has not been conclusive evidence for prevention of brain atrophy by anti-dementia drugs in mild cognitive impairment and Alzheimer's Disease. Methods: Relevant studies were identified through searches of PubMed, databases of the Cochrane Library, and PsycINFO citations up to 16 May, 2015. Only double-blind, randomized, placebo-controlled clinical trials of anti-dementia drugs in patients with mild cognitive impairment or Alzheimer's Disease were included. Primary outcomes were annualized percent change of total brain volume (% TBV/y), annualized percent change of hippocampal volume (% HV/y), and annualized percent change of ventricular volume (% VV/y) measured by magnetic resonance imaging. Standardized mean difference (SMD) and 95% confidence intervals (CI) were calculated for relevant outcomes. Results: Seven randomized, placebo-controlled clinical trials (n = 1708) were found to meet the inclusion criteria, including 4 mild cognitive impairment studies (n = 1327) and 3 Alzheimer's Disease studies (n = 381) [ 3 donepezil studies (2 mild cognitive impairment studies and 1 Alzheimer's Disease study), 1 galantaime study for mild cognitive impairment, 2 mementine studies for Alzheimer's Disease, and 1 rivastigmine study for mild cognitive impairment]. Pooled anti-dementia drugs showed superior protective outcomes compared with placebo regarding % TBV/y (SMD = -0.21, 95% CI = -0.37 to -0.04, P =.01, N = 4, n = 624) and % VV/y (SMD = -0.79, 95% CI = -1.40 to -0.19, P =.01, N = 3, n = 851). However, % HV/y failed to show difference between both groups. Among anti-dementia drugs, donepezil showed significantly greater protective effects than placebo regarding % TBV/y (SMD = -0.43, 95% CI = -0.74 to -0.12, P =.007, N = 1, n = 164) and % VV/y (SMD = -0.51, 95% CI = -0.73 to -0.29, P <.00001, N = 2, n = 338). Rivastigmine was also superior to placebo regarding % VV/y (SMD = -1.33, 95% CI = -1.52 to -1.14, P <.00001). Conclusions: The results favored the hypothesis that anti-dementia drugs may prevent brain atrophy in patients with mild cognitive impairment and Alzheimer's Disease.

持続性注射剤は服薬アドヒアランス不良、再発を繰り返している統合失調症患者に対して、有効な治療法であることが示唆されている。Aripiprazole once-monthly(AOM)は持続性注射剤の中で初めてdopamine partial agonist作用を有する薬剤である。AOMは無作為割付試験の結果から、有効性評価項目ではプラセボ群と比べて、急性期では陽性症状、陰性症状、社会機能障害の改善を示した。維持期では再発予防および脱落までの期間を延長させた。またAOM群は経口aripiprazole群と比べて維持期における脱落率が低く、脱落までの期間を延長させる可能性が示唆された。安全性評価項目において急性期では、AOM群はプラセボ群と比べて体重増加を認めたが、維持期ではプラセボ群、経口aripiprazole群と変わらなかった。錐体外路症状は、急性期、維持期どちらにおいてもAOM群はプラセボ群、経口aripiprazole群と変わらなかった。これらより、AOMは有効性、安全性に優れた薬剤であることが示唆された。(著者抄録)

Objective: We conducted a systematic review and meta-analysis of the efficacy of aripiprazole once monthly (AOM) for schizophrenia. Methods: Randomized controlled trials (RCTs) on AOM, published until June 25, 2015, were retrieved from PubMed, Cochrane, and PsycINFO databases. Relative risk (RR), standardized mean difference (SMD), 95% confidence intervals (95% CIs), and numbers needed to treat/harm (NNT/NNH) were calculated. Results: We identified four relevant RCTs (total n=1,860), two placebo-controlled trials, one noninferiority trial comparing AOM to oral aripiprazole (OA), and one including therapeutic doses of AOM and OA, as well as an AOM dose below therapeutic threshold (control arm). AOM was superior to placebo for decreasing Positive and Negative Syndrome Scale (PANSS) total scores (SMD =-0.65, 95% CI =-0.90 to -0.41, n=1,126). However, PANSS total scores did not differ significantly between pooled AOM and OA groups. The pooled AOM group showed significantly lower incidence of all-cause discontinuation (RR =0.54, 95% CI =0.41-0.71, n=1,139, NNH =4) and inefficacy (RR =0.28, 95% CI =0.21 -0.38, n=1,139, NNH =5) than placebo, but was not superior to placebo regarding discontinuation due to adverse events (AEs) or death. The AOM group exhibited a lower incidence of all-cause discontinuation than OA (RR =0.78, 95% CI =0.64-0.95, n=986, NNH =14), but there were no intergroup differences in discontinuation due to inefficacy, AEs, or death. There were no significant differences in extrapyramidal symptoms scale scores between AOM and placebo or between AOM and OA. AOM resulted in higher weight gain than placebo (SMD =0.41, 95% CI =0.18-0.64, n=734) but lower than OA (SMD =-0.16, 95% CI =-0.29 to -0.02, n=847). Conclusion: AOM has antipsychotic efficacy and low risk of discontinuation due to AEs.

ObjectiveThis study aimed to perform a comprehensive meta-analysis of minocycline augmentation therapy in patients with schizophrenia receiving antipsychotic agents. MethodsData published up to 2 June 2014 were obtained from the PubMed, PsycINFO, Google Scholar, and Cochrane Library databases. We conducted a systematic review and meta-analysis of patient data from randomized controlled trials (RCTs) comparing minocycline with placebo. Relative risk (RR), standardized mean difference (SMD), and 95% confidence intervals were calculated. ResultsWe included four RCTs. The total sample included 330 patients. Minocycline was superior to placebo for decreasing Positive and Negative Syndrome Scale (PANSS) total scores (SMD=-0.70), PANSS negative subscale scores (SMD=-0.86), and PANSS general subscale scores (SMD=-0.50) but was not different from placebo for PANSS positive subscale scores (SMD=-0.26) and depressive symptoms (SMD=-0.28). Minocycline was equivalent to placebo for all-cause discontinuation (RR=1.10), discontinuation due to inefficacy (RR=0.42), discontinuation due to adverse events (RR=1.56), and discontinuation due to death (RR=3.18). Minocycline was superior to placebo for extrapyramidal side-effect scores (SMD=-0.32). ConclusionsMinocycline may improve the psychopathology of schizophrenia, especially the negative symptoms, and seems to be well tolerated. Copyright (c) 2014 John Wiley & Sons, Ltd.